- Email: [email protected]
VALUE OF ELECTROENCEPHALOGRAPHY IN AIDS
1047
TREATMENT OF SALMONELLA TYPHI CARRIER STATE WITH CIPROFLOXACIN
SIR,-We should like to report the successful treatment of a faecal carrier of Salmonella typhi with ciprofloxacin, one of the new quinolone agents. The patient was a 59-year-old Spanish woman, resident in the UK for over 20 years. During screening of faeces from food handlers associated with an outbreak of food poisoning due to S typhimurium, she was found to be persistently excreting S typhi over a period of 6 weeks. There was no history of enteric fever or typhoid immunisation. She was generally in good health, apart from having dyspepsia relieved by antacids. Abdominal ultrasound and oral cholecystogram revealed gallstones. Her husband was a food handler and S typhi of the same phage type (El) as the strain isolated from his wife was present in one of thirty faecal samples provided by him. It seemed likely that this single positive sample was in some way derived from his wife, possibly by perineal soiling. Since there was a continuing risk of this contamination, and in view of his occupation, cholecystectomy was suggested to but declined by the wife. However, she agreed to antimicrobial therapy. Because of penicillin allergy co-trimoxazole was given initially, but she reacted to it with a rash and vomiting. The organism was sensitive to ciprofloxacin (MIC 0-016 mg/1), which was given in a dose of 750 mg by mouth for 28 days on an outpatient basis. There were no-side-effects and haematological and biochemical variables monitored weekly during treatment remained normal. Since the completion of treatment 4 months ago S typhi has not been isolated from any of twenty-one specimens of faeces. The S typhi carrier state has been treated successfully with ampicillin 1-4 or co-trimoxazole,s usually with high doses over long periods, but we were not able to give these agents to our patient. Where there is co-existing biliary pathology antimicrobial therapy alone has not always been effective.Our experience suggests that ciprofloxacin, which has an MIC of 0 -008-0’03 mg/1, may be
effective7
Department of Microbiology, Newcastle General Hospital, Newcastle upon Tyne
S. J. HUDSON H. R. INGHAM M. H. SNOW
1 Christie AB. Treatment of typhoid carriers with ampicillin. Br Med J 1964; i: 1609-11. 2 Whitby JMF. Ampicillin in treatment of Salmonella ryphi carriers. Lancet 1964; ii: 71-72.
3 Russell EM, Sutherland A, Walker W. Ampicillin for persistent typhoid excretors, including a clinical trial in convalescence. Br Med J 1966; ii: 555-57. 4 Phillips WE Treatment of chronic typhoid carriers with ampicillin. JAMA 1971; 217: 913-15 5 Brodie J, Macqueen IA, Livingstone D Effect of trimethoprim-sulphamethoxazole on typhoid and salmonella carriers. Br Med J 1970; iii: 318-19. 6 Dinbar A, Altmann MS, Tulcinsky DB. The treatment of chronic biliary salmonella
Am J Med 1969; 47: 236-42. DS, Bywater MJ, Holt HA, White LO. In-vitro studies with ciprofloxacin, new 4-quinolone compound. J Antimicrob Chemother 1984; 13: 333-46. carriers.
7 Reeves
a
HTLV-III ANTIBODY SCREENING IN GERMAN BLOOD DONORS
SIR,-Epidemiological data suggest that the human T-lymphotropic retrovirus type III (HTLV-III) can be transmitted by blood and blood products so blood donor screening for HTLV-III antibodies may be one way of preventing the spread of the virus into the general population. Considerable effort has been put into the development of screening tests for HTLV-III antibodies. In early March, 1985, two commercial tests were licensed by the US Food and Drug Administration. We report here the results ofapilot study with an enzyme immunoassay (Abbott) in German blood donors between December, 1984, and February, 1985. Some of these data were mentioned at a meeting in London on April 3 and were referred to in your April 13 editorial (p 856). The assay was done following the instructions of the manufacturer" washing and determination of absorption at 492 nm being done with their automated equipment (’Quantawash’ and ’Quantumatic’). In a first phase, inter-assay and intra-assay reproducibility were checked with the aid of two panels of 20 specimens each. The results were found to be within the expected range. In the subsequent random donor study, 4511 donors were asked to participate;
66 refused and 195 were not interested in the results of the examination. The specimens of 4445 consenting blood donors of both sexes aged 18-65 years from Hesse, were kept at 4°C and tested within 24 h of donation. All specimens with absorption above the cut off value in the first run were considered as "reactive". If the absorption values were within 10% of the calculated cut-off, samples within this 20% range were assigned to a "grey zone" for the purpose of this pilot study (the Abbott kit as marketed provides for a negative or positive result only). Only repeatably reactive specimens were considered "positive". 4390 donor samples (98 - 76%) were negative in the first run and were not tested further. Altogether 46/4445 specimens (1-03%) were reactive (optical density at 492 nm greater than cut-off) in the first run; 21 specimens (0 - 47%) were reactive after the repeat run. 15 of these 21 samples (0 -34%) had absorption values above the grey zone; 6 were in the grey zone. This means that 1 out of 212 blood units was not issued for blood transfusion. The percentage of HTLV-III antibody positivity among blood donors in Hesse is a little lower than the 0052% (out of 6720 blood donors from six German cities) reported for an ELISA developed in Schneider and colleagues’ laboratory.! Weiss et al2 found 4/228 (1- 75%) positive donors in Burlington/Vermont (sampling in 1981) with their ELISA test with its cut-off at a ratio of 4-99). Cheingsong-Popov et a13 detected no HTLV-III positive donors among 1042 individuals from the UK, using a competitive RIA. A second blood sample was requested from 21 positive or doubtful positive donors; 15 were reinvestigated 6-8 weeks after the first donation. Two different assay batches (HTLV-III EIA CML 9 and 74089 HR) were used and 7/11 previously positive donors were positive again; 4 were negative. Reinvestigation of 4 grey-zone specimens yielded 2 negative results and 2 positive. These differences between the first and second bleedings may be explained by inherent test variability and/or decreasing antibody levels. All positive samples will now be investigated in confirmatory tests (western blot, radioimmunoprecipitation, and immunofluorescence). Since a certain fraction of false positive results may be expected with any screening procedure in a low-risk population, we will inform only those donors whose specimens are found repeatably positive in the ELISA and positive in a confirmatory test. The small fraction of random blood donor specimens found repeatably positive indicates the usefulness of this test for blood donor screening; the number of deferrable blood units would not affect the supply of blood and blood products in our institution. To reduce the risk of HTLV-III transmission by blood products, donor screening is one important measure; an appeal to members of the known risk groups to refrain from giving blood is another. Institute of Immunohaematology, University of Frankfurt, and Red Cross Blood Transfusion Service Hessen, D-6000 Frankfurt-am-Main, West Germany
S. SEIDL P. KÜHNL
1. Schneider
J, Hayei H, Bienzle U, et al. Antibodies to HTLV-III in German blood donors. Lancet 1985; i: 275-76. 2. Weiss SH, Goedert JJ, Sarngadharan MG, et al. Screening test for HTLV-III (AIDS agent) antibodies Specificity, sensitivity, and applications. JAMA 1985; 253: 221-25. 3. Cheingsong-Popov RC, Weiss RA, Dalgleish A, et al. Prevalence of antibody to human T-lymphotropic virus type III in AIDS and AIDS risk patients in Britain. Lancet 1984; ii: 477-80.
VALUE OF ELECTROENCEPHALOGRAPHY IN AIDS
SIR,-Neurological complications of AIDS are now well and the neurotropism of the virus thought to cause AIDS supports the probability of the existence of a chronic AIDS encephalopathy.3In our AIDS outpatient clinic in Frankfurt we have, between October, 1983, and January, 1985, neurologically examined 26 male homosexuals with AIDS or persistent generalised lymphadenopathy (PGL). The examination included electroencephalography (EEG), and 13 patients (50%) had a slow alpha basal activity (8-9 Hz). This frequency is much higher than the 10-15% reported in normal adults.4,5 5 out of these 13 patients have since acquired an acute or subacute encephalitis (usually toxo-
recognised’2
1048
plasma encephalitis).5,6 8 have persistent slow alpha basal activity usually combined with a mild organic psycho-syndrome, and these AIDS patients may have a chronic encephalopathy, possibly due to the AIDS virus. EEG should be done routinely in all patients with AIDS or PGL. It may provide important information on the early stages of encephalopathy, perhaps even before the encephalopathy becomes clinically apparent. A combination of EEG and neuropsychological tests might be even more helpful. Follow-up studies are needed to evaluate the significance of these EEG findings for the prognosis. W. ENZENSBERGER P.-A. FISCHER E. B. HELM W. STILLE
Departments of Neurology and Internal Medicine,
University Hospital Frankfurt, D-6000 Frankfurt 71, West Germany
RG, Conley FK, McCabe RE, Remington JS. Toxoplasmic encephalitis in patients with acquired immune deficiency syndrome. JAMA 1984;
1. Luft BJ, Brooks
252: 913-17. 2. Snider WD, Simpson
DM, Nielsen S, Gold JWM, Metroka CE, Posner JB. Neurological complications of acquired immune deficiency syndrome: analysis of 50 patients. Ann Neurol 1983; 14: 403-18. 3. Shaw GM, Harper ME, Hahn BH, et al. Infection in brains of children and adults with AIDS encephalopathy. Science 1985; 227: 177-81 4. Christian W. Klinische Elektroenzephalographie. Stuttgart: Thieme, 1982. 5. Enzensberger W, Helm EB, Fischer P-A. EEG follow-up examinations in AIDSpatients. J Electroencephalogr Clin Neurophysiol (in press). 6. Enzensberger W, Helm EB, Hopp G, Stille W, Fischer P-A. Toxoplasmoseenzephalitis bei Patienten mit AIDS. Dt Med Wochenschr 1985; 110: 83-87.
increase in neopterin. Determination of urinary neopterin alone cannot be a specific marker for AIDS. However, it may be useful in the follow-up of HTLV-III seropositive symptomless individuals.
Supported in part by grants from Consiglio Nazionale delle Ricerche, Associazione Italiana per la Ricerca sul Cancro and Ministero della Sanita. Laboratory of
Clinical Pathology, G. Pascale Foundation Tumour Institute, Naples
M. PERNA F. NITSCH
Section of Experimental G. Pascale Foundation Tumour Institute
G. SANTELLI A. MARFELLA
Pharmacology,
Division of Viral Oncology, G. Pascale Foundation Tumour Institute, 80131 Naples, Italy
G. GIRALDO E. BETH-GIRALDO
Division of Medicine, Cancer Research Institute, UCSF School of Medicine, San Francisco, California, USA
J. A. LEVY
2nd Infectious Disease Clinic, University of Naples
M. PIAZZA R. DE MERCATO A. CHIRIANNI P. T. CATALDO E. GIULIANO
Department of Dermatology, Cardarelli Hospital, Naples
R. COZZI
Leeming RG, Brown SM, Blair JA. Regulation of pterin synthesis. Arch Fr Pediatr 1983; 40: 223-25. 2. Huber C, Fuchs D, Hausen A, et al. Pteridines as a new marker to detect human T-cell activated by allogeneic or modified self major histocompatibility complex (MHC) 1.
URINARY NEOPTERIN, A USEFUL MARKER FOR AIDS?
determinants.J Immunol 1983; 130: 1047-50. C, Bachtelor JR, Fuchs D, et al. Immune response-associated production of neopterin. J Exp Med 1984; 160: 310-16. Wachter H, Hausen A, Grabmayr K, et al. Ausscheidung von Neopterin im Harn von Pazienten mit malignen Tumoren und mit Viruserkraukungen. Hoppe-Seyler’s Z Physiol Chem 1979; 360: 1957-60. Wachter H, Fuchs D, Hausen A, et al. Elevated urinary neopterin levels in patients with the acquired immunodeficiency syndrome (AIDS). Hoppe-Seyler’s Z Physiol
3. Huber
SIR,-Neopterin is an intermediate in the biosynthesis of tetrahydrobiopterin (BH4), an essential co-factor for tyrosine and tryptophan hydroxylation. BH4 plays an important role in the biosynthesis of catecholamines and sero’tonin.1 Moreover, neopterin may be an in-vitro indicator of activation of the immune
system.2
Its raised excretion has been related to the action of interferons on the T-lymphocyte/macrophage axis.3 Increased urinary neopterin levels have been observed in patients with malignancies and viral diseases4 and patients with acquired immunodeficiency syndrome (AIDS) and generalised lymphadenopathy.5,6 We have investigated the role of this marker in unselected subjects with a history of intravenous drug abuse, a population at high risk for AIDS or AIDS-related complex. 40 drug addicts aged 18-36 (mean 25) were analysed, of whom 33 were symptom-free, 6 had lymphadenopathy, and 1 had AIDS associated with opportunistic infections. They presented themselves voluntarily to the Naples Study Group on AIDS/KS (set up in May, 1984). The controls were 15 healthy subjects aged 22-40 (mean 31), matched by sex and geographical location.
Urinary neopterin levels were measured by Hausen’s method’ in a liquid chromatograph (’Varian 5500 LC’) with ultraviolet and fluorescence detectors for simultaneous measurement of neopterin and creatinine. Results were expressed in pmol/mol creatinine by a computerised ’Varian Vista 402’ data system. Antibodies to AIDS-associated retrovirus (ARV/HTLV-III) were determined by indirect immunofluorescence on an ARV-infected human T cell line, designated EI1/HUT-78 and specificity was controlled on noninfected HUT-78 cells.’
Urinary neopterin in controls (111’ 3±23 1 mol/mol creatinine) accorded with values obtained by others,9 and all controls were HTLV-III seronegative. All 7 drug abusers with symptoms had neopterin levels above 195 J..lmollmol compared with 7 of 33 symptomless drug addicts and none of the controls. Moreover, all 7 addicts with symptoms were also seropositive for ARV/HTLV-III while only 3 of the 33 symptomless drug abusers were HTLV-III seropositive and 1 had an increase in neopterin excretion. Persistently raised levels of circulating interferon-a2 seem to have prognostic value in predicting the development of AIDS in patients with lymphadenopathy. JO Moreover, IFN-a2 and y producing T cells and macrophages appear to be involved in the production and/or controlofneopterin excretion. Human IFN-a2in doses above 5 million units within 24 h induced a sharp increase in neopterin in 5 of 5 cancer patients.3Perhaps T-helper cell lysis induced by HTLVIII with reactive production of lymphokines such as IFN leads to an
4.
5.
Chem 1983; 364: 1345-46. D, Hausen A, Reibnegger G, et al. Urinary neopterin in the diagnosis of AIDS. Europ J Clin Microbiol 1984; 3: 70-71. 7. Hausen A, Fuchs D, König K, et al. Determination of neopterin in human urine by reversed-phase high performance liquid chromatography. J Chromatogr 1982; 227:
6. Fuchs
61-70.
8. 9.
Levy JA, Hoffman AD, Kramer SM, et al. Isolation of lymphocytopathic retroviruses from San Francisco patients with AIDS. Science 1984; 225: 840-42. Hausen A, Wachter H. Pteridines in the assessment of neoplasia. J Clin Chem Clin
Bioch 1982; 20: 593-602. 10. Buimovici-Klein E, Lange M, Cooper LZ, et al. Is presence of interferon predictive AIDS? Lancet 1983; ii: 344
for
DOUBLE-BLIND SHORT-TERM TRIAL OF FURAZOLIDONE IN PEPTIC ULCER
SIR,-In the treatment of peptic ulcer antacids and anticholinergic drugs are not satisfactory and, though cimetidine achieves a high healing rate, the relapse rate is also high. We have been using furazolidone for peptic ulcer since 1978, with good results in both the short and long term,I,2 and we report here a double-blind trial of this drug in 70 cases of peptic ulcer seen between November, 1982, and May, 1983. 70 patients with endoscopically confirmed peptic ulcer with upper abdominal pain and/or upper gastrointestinal bleeding (54 inpatients, 15 outpatients) were allocated at random to furazolidone treatment
(F) or placebo (P):
If there was gastrointestinal bleeding treatment was delayed until it had stopped. The furazolidone dose was 200 mgx4daily for 4 days, then 200 mg x 3 for 3 days, and finally 100 mgx4for 7 days. Fibreoptic endoscopy was repeated at the end of therapy. Ulcer "healing" was defined by the disappearing of ulceration or the presence of scarring; "progress" was defined as a reduction in ulcer
TREATMENT OF SALMONELLA TYPHI CARRIER STATE WITH CIPROFLOXACIN
SIR,-We should like to report the successful treatment of a faecal carrier of Salmonella typhi with ciprofloxacin, one of the new quinolone agents. The patient was a 59-year-old Spanish woman, resident in the UK for over 20 years. During screening of faeces from food handlers associated with an outbreak of food poisoning due to S typhimurium, she was found to be persistently excreting S typhi over a period of 6 weeks. There was no history of enteric fever or typhoid immunisation. She was generally in good health, apart from having dyspepsia relieved by antacids. Abdominal ultrasound and oral cholecystogram revealed gallstones. Her husband was a food handler and S typhi of the same phage type (El) as the strain isolated from his wife was present in one of thirty faecal samples provided by him. It seemed likely that this single positive sample was in some way derived from his wife, possibly by perineal soiling. Since there was a continuing risk of this contamination, and in view of his occupation, cholecystectomy was suggested to but declined by the wife. However, she agreed to antimicrobial therapy. Because of penicillin allergy co-trimoxazole was given initially, but she reacted to it with a rash and vomiting. The organism was sensitive to ciprofloxacin (MIC 0-016 mg/1), which was given in a dose of 750 mg by mouth for 28 days on an outpatient basis. There were no-side-effects and haematological and biochemical variables monitored weekly during treatment remained normal. Since the completion of treatment 4 months ago S typhi has not been isolated from any of twenty-one specimens of faeces. The S typhi carrier state has been treated successfully with ampicillin 1-4 or co-trimoxazole,s usually with high doses over long periods, but we were not able to give these agents to our patient. Where there is co-existing biliary pathology antimicrobial therapy alone has not always been effective.Our experience suggests that ciprofloxacin, which has an MIC of 0 -008-0’03 mg/1, may be
effective7
Department of Microbiology, Newcastle General Hospital, Newcastle upon Tyne
S. J. HUDSON H. R. INGHAM M. H. SNOW
1 Christie AB. Treatment of typhoid carriers with ampicillin. Br Med J 1964; i: 1609-11. 2 Whitby JMF. Ampicillin in treatment of Salmonella ryphi carriers. Lancet 1964; ii: 71-72.
3 Russell EM, Sutherland A, Walker W. Ampicillin for persistent typhoid excretors, including a clinical trial in convalescence. Br Med J 1966; ii: 555-57. 4 Phillips WE Treatment of chronic typhoid carriers with ampicillin. JAMA 1971; 217: 913-15 5 Brodie J, Macqueen IA, Livingstone D Effect of trimethoprim-sulphamethoxazole on typhoid and salmonella carriers. Br Med J 1970; iii: 318-19. 6 Dinbar A, Altmann MS, Tulcinsky DB. The treatment of chronic biliary salmonella
Am J Med 1969; 47: 236-42. DS, Bywater MJ, Holt HA, White LO. In-vitro studies with ciprofloxacin, new 4-quinolone compound. J Antimicrob Chemother 1984; 13: 333-46. carriers.
7 Reeves
a
HTLV-III ANTIBODY SCREENING IN GERMAN BLOOD DONORS
SIR,-Epidemiological data suggest that the human T-lymphotropic retrovirus type III (HTLV-III) can be transmitted by blood and blood products so blood donor screening for HTLV-III antibodies may be one way of preventing the spread of the virus into the general population. Considerable effort has been put into the development of screening tests for HTLV-III antibodies. In early March, 1985, two commercial tests were licensed by the US Food and Drug Administration. We report here the results ofapilot study with an enzyme immunoassay (Abbott) in German blood donors between December, 1984, and February, 1985. Some of these data were mentioned at a meeting in London on April 3 and were referred to in your April 13 editorial (p 856). The assay was done following the instructions of the manufacturer" washing and determination of absorption at 492 nm being done with their automated equipment (’Quantawash’ and ’Quantumatic’). In a first phase, inter-assay and intra-assay reproducibility were checked with the aid of two panels of 20 specimens each. The results were found to be within the expected range. In the subsequent random donor study, 4511 donors were asked to participate;
66 refused and 195 were not interested in the results of the examination. The specimens of 4445 consenting blood donors of both sexes aged 18-65 years from Hesse, were kept at 4°C and tested within 24 h of donation. All specimens with absorption above the cut off value in the first run were considered as "reactive". If the absorption values were within 10% of the calculated cut-off, samples within this 20% range were assigned to a "grey zone" for the purpose of this pilot study (the Abbott kit as marketed provides for a negative or positive result only). Only repeatably reactive specimens were considered "positive". 4390 donor samples (98 - 76%) were negative in the first run and were not tested further. Altogether 46/4445 specimens (1-03%) were reactive (optical density at 492 nm greater than cut-off) in the first run; 21 specimens (0 - 47%) were reactive after the repeat run. 15 of these 21 samples (0 -34%) had absorption values above the grey zone; 6 were in the grey zone. This means that 1 out of 212 blood units was not issued for blood transfusion. The percentage of HTLV-III antibody positivity among blood donors in Hesse is a little lower than the 0052% (out of 6720 blood donors from six German cities) reported for an ELISA developed in Schneider and colleagues’ laboratory.! Weiss et al2 found 4/228 (1- 75%) positive donors in Burlington/Vermont (sampling in 1981) with their ELISA test with its cut-off at a ratio of 4-99). Cheingsong-Popov et a13 detected no HTLV-III positive donors among 1042 individuals from the UK, using a competitive RIA. A second blood sample was requested from 21 positive or doubtful positive donors; 15 were reinvestigated 6-8 weeks after the first donation. Two different assay batches (HTLV-III EIA CML 9 and 74089 HR) were used and 7/11 previously positive donors were positive again; 4 were negative. Reinvestigation of 4 grey-zone specimens yielded 2 negative results and 2 positive. These differences between the first and second bleedings may be explained by inherent test variability and/or decreasing antibody levels. All positive samples will now be investigated in confirmatory tests (western blot, radioimmunoprecipitation, and immunofluorescence). Since a certain fraction of false positive results may be expected with any screening procedure in a low-risk population, we will inform only those donors whose specimens are found repeatably positive in the ELISA and positive in a confirmatory test. The small fraction of random blood donor specimens found repeatably positive indicates the usefulness of this test for blood donor screening; the number of deferrable blood units would not affect the supply of blood and blood products in our institution. To reduce the risk of HTLV-III transmission by blood products, donor screening is one important measure; an appeal to members of the known risk groups to refrain from giving blood is another. Institute of Immunohaematology, University of Frankfurt, and Red Cross Blood Transfusion Service Hessen, D-6000 Frankfurt-am-Main, West Germany
S. SEIDL P. KÜHNL
1. Schneider
J, Hayei H, Bienzle U, et al. Antibodies to HTLV-III in German blood donors. Lancet 1985; i: 275-76. 2. Weiss SH, Goedert JJ, Sarngadharan MG, et al. Screening test for HTLV-III (AIDS agent) antibodies Specificity, sensitivity, and applications. JAMA 1985; 253: 221-25. 3. Cheingsong-Popov RC, Weiss RA, Dalgleish A, et al. Prevalence of antibody to human T-lymphotropic virus type III in AIDS and AIDS risk patients in Britain. Lancet 1984; ii: 477-80.
VALUE OF ELECTROENCEPHALOGRAPHY IN AIDS
SIR,-Neurological complications of AIDS are now well and the neurotropism of the virus thought to cause AIDS supports the probability of the existence of a chronic AIDS encephalopathy.3In our AIDS outpatient clinic in Frankfurt we have, between October, 1983, and January, 1985, neurologically examined 26 male homosexuals with AIDS or persistent generalised lymphadenopathy (PGL). The examination included electroencephalography (EEG), and 13 patients (50%) had a slow alpha basal activity (8-9 Hz). This frequency is much higher than the 10-15% reported in normal adults.4,5 5 out of these 13 patients have since acquired an acute or subacute encephalitis (usually toxo-
recognised’2
1048
plasma encephalitis).5,6 8 have persistent slow alpha basal activity usually combined with a mild organic psycho-syndrome, and these AIDS patients may have a chronic encephalopathy, possibly due to the AIDS virus. EEG should be done routinely in all patients with AIDS or PGL. It may provide important information on the early stages of encephalopathy, perhaps even before the encephalopathy becomes clinically apparent. A combination of EEG and neuropsychological tests might be even more helpful. Follow-up studies are needed to evaluate the significance of these EEG findings for the prognosis. W. ENZENSBERGER P.-A. FISCHER E. B. HELM W. STILLE
Departments of Neurology and Internal Medicine,
University Hospital Frankfurt, D-6000 Frankfurt 71, West Germany
RG, Conley FK, McCabe RE, Remington JS. Toxoplasmic encephalitis in patients with acquired immune deficiency syndrome. JAMA 1984;
1. Luft BJ, Brooks
252: 913-17. 2. Snider WD, Simpson
DM, Nielsen S, Gold JWM, Metroka CE, Posner JB. Neurological complications of acquired immune deficiency syndrome: analysis of 50 patients. Ann Neurol 1983; 14: 403-18. 3. Shaw GM, Harper ME, Hahn BH, et al. Infection in brains of children and adults with AIDS encephalopathy. Science 1985; 227: 177-81 4. Christian W. Klinische Elektroenzephalographie. Stuttgart: Thieme, 1982. 5. Enzensberger W, Helm EB, Fischer P-A. EEG follow-up examinations in AIDSpatients. J Electroencephalogr Clin Neurophysiol (in press). 6. Enzensberger W, Helm EB, Hopp G, Stille W, Fischer P-A. Toxoplasmoseenzephalitis bei Patienten mit AIDS. Dt Med Wochenschr 1985; 110: 83-87.
increase in neopterin. Determination of urinary neopterin alone cannot be a specific marker for AIDS. However, it may be useful in the follow-up of HTLV-III seropositive symptomless individuals.
Supported in part by grants from Consiglio Nazionale delle Ricerche, Associazione Italiana per la Ricerca sul Cancro and Ministero della Sanita. Laboratory of
Clinical Pathology, G. Pascale Foundation Tumour Institute, Naples
M. PERNA F. NITSCH
Section of Experimental G. Pascale Foundation Tumour Institute
G. SANTELLI A. MARFELLA
Pharmacology,
Division of Viral Oncology, G. Pascale Foundation Tumour Institute, 80131 Naples, Italy
G. GIRALDO E. BETH-GIRALDO
Division of Medicine, Cancer Research Institute, UCSF School of Medicine, San Francisco, California, USA
J. A. LEVY
2nd Infectious Disease Clinic, University of Naples
M. PIAZZA R. DE MERCATO A. CHIRIANNI P. T. CATALDO E. GIULIANO
Department of Dermatology, Cardarelli Hospital, Naples
R. COZZI
Leeming RG, Brown SM, Blair JA. Regulation of pterin synthesis. Arch Fr Pediatr 1983; 40: 223-25. 2. Huber C, Fuchs D, Hausen A, et al. Pteridines as a new marker to detect human T-cell activated by allogeneic or modified self major histocompatibility complex (MHC) 1.
URINARY NEOPTERIN, A USEFUL MARKER FOR AIDS?
determinants.J Immunol 1983; 130: 1047-50. C, Bachtelor JR, Fuchs D, et al. Immune response-associated production of neopterin. J Exp Med 1984; 160: 310-16. Wachter H, Hausen A, Grabmayr K, et al. Ausscheidung von Neopterin im Harn von Pazienten mit malignen Tumoren und mit Viruserkraukungen. Hoppe-Seyler’s Z Physiol Chem 1979; 360: 1957-60. Wachter H, Fuchs D, Hausen A, et al. Elevated urinary neopterin levels in patients with the acquired immunodeficiency syndrome (AIDS). Hoppe-Seyler’s Z Physiol
3. Huber
SIR,-Neopterin is an intermediate in the biosynthesis of tetrahydrobiopterin (BH4), an essential co-factor for tyrosine and tryptophan hydroxylation. BH4 plays an important role in the biosynthesis of catecholamines and sero’tonin.1 Moreover, neopterin may be an in-vitro indicator of activation of the immune
system.2
Its raised excretion has been related to the action of interferons on the T-lymphocyte/macrophage axis.3 Increased urinary neopterin levels have been observed in patients with malignancies and viral diseases4 and patients with acquired immunodeficiency syndrome (AIDS) and generalised lymphadenopathy.5,6 We have investigated the role of this marker in unselected subjects with a history of intravenous drug abuse, a population at high risk for AIDS or AIDS-related complex. 40 drug addicts aged 18-36 (mean 25) were analysed, of whom 33 were symptom-free, 6 had lymphadenopathy, and 1 had AIDS associated with opportunistic infections. They presented themselves voluntarily to the Naples Study Group on AIDS/KS (set up in May, 1984). The controls were 15 healthy subjects aged 22-40 (mean 31), matched by sex and geographical location.
Urinary neopterin levels were measured by Hausen’s method’ in a liquid chromatograph (’Varian 5500 LC’) with ultraviolet and fluorescence detectors for simultaneous measurement of neopterin and creatinine. Results were expressed in pmol/mol creatinine by a computerised ’Varian Vista 402’ data system. Antibodies to AIDS-associated retrovirus (ARV/HTLV-III) were determined by indirect immunofluorescence on an ARV-infected human T cell line, designated EI1/HUT-78 and specificity was controlled on noninfected HUT-78 cells.’
Urinary neopterin in controls (111’ 3±23 1 mol/mol creatinine) accorded with values obtained by others,9 and all controls were HTLV-III seronegative. All 7 drug abusers with symptoms had neopterin levels above 195 J..lmollmol compared with 7 of 33 symptomless drug addicts and none of the controls. Moreover, all 7 addicts with symptoms were also seropositive for ARV/HTLV-III while only 3 of the 33 symptomless drug abusers were HTLV-III seropositive and 1 had an increase in neopterin excretion. Persistently raised levels of circulating interferon-a2 seem to have prognostic value in predicting the development of AIDS in patients with lymphadenopathy. JO Moreover, IFN-a2 and y producing T cells and macrophages appear to be involved in the production and/or controlofneopterin excretion. Human IFN-a2in doses above 5 million units within 24 h induced a sharp increase in neopterin in 5 of 5 cancer patients.3Perhaps T-helper cell lysis induced by HTLVIII with reactive production of lymphokines such as IFN leads to an
4.
5.
Chem 1983; 364: 1345-46. D, Hausen A, Reibnegger G, et al. Urinary neopterin in the diagnosis of AIDS. Europ J Clin Microbiol 1984; 3: 70-71. 7. Hausen A, Fuchs D, König K, et al. Determination of neopterin in human urine by reversed-phase high performance liquid chromatography. J Chromatogr 1982; 227:
6. Fuchs
61-70.
8. 9.
Levy JA, Hoffman AD, Kramer SM, et al. Isolation of lymphocytopathic retroviruses from San Francisco patients with AIDS. Science 1984; 225: 840-42. Hausen A, Wachter H. Pteridines in the assessment of neoplasia. J Clin Chem Clin
Bioch 1982; 20: 593-602. 10. Buimovici-Klein E, Lange M, Cooper LZ, et al. Is presence of interferon predictive AIDS? Lancet 1983; ii: 344
for
DOUBLE-BLIND SHORT-TERM TRIAL OF FURAZOLIDONE IN PEPTIC ULCER
SIR,-In the treatment of peptic ulcer antacids and anticholinergic drugs are not satisfactory and, though cimetidine achieves a high healing rate, the relapse rate is also high. We have been using furazolidone for peptic ulcer since 1978, with good results in both the short and long term,I,2 and we report here a double-blind trial of this drug in 70 cases of peptic ulcer seen between November, 1982, and May, 1983. 70 patients with endoscopically confirmed peptic ulcer with upper abdominal pain and/or upper gastrointestinal bleeding (54 inpatients, 15 outpatients) were allocated at random to furazolidone treatment
(F) or placebo (P):
If there was gastrointestinal bleeding treatment was delayed until it had stopped. The furazolidone dose was 200 mgx4daily for 4 days, then 200 mg x 3 for 3 days, and finally 100 mgx4for 7 days. Fibreoptic endoscopy was repeated at the end of therapy. Ulcer "healing" was defined by the disappearing of ulceration or the presence of scarring; "progress" was defined as a reduction in ulcer